Porphyria
Despite its rarity, acute intermittent porphyria (AIP) has been the subject of extensive research over the years, with a particular focus on the development of animal models to study the disease and test potential therapies. Our company's AIP mouse models and disease modeling services offer researchers a powerful tool for studying the disease and identifying new therapeutic targets. With our expertise in animal genetics and breeding and our commitment to advancing AIP research, we are well-positioned to support researchers in their AIP efforts.
Background
AIP is a rare genetic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, which encodes an enzyme involved in the heme biosynthesis pathway. Deficiency of the enzyme leads to the accumulation of porphyrins or porphyrin precursors in tissues, blood, or urine and manifests as severe abdominal pain, neuropsychiatric symptoms, and in some cases, life-threatening acute attacks.
Although AIP is a challenging disease to study because of its rarity and complex pathophysiology, animal models have proven to be invaluable in advancing our understanding of the disease and developing new therapies. AIP mouse models have been shown to provide profound insights into the disease pathogenesis of AIP nerve injury. They are also valuable for the preclinical evaluation of RNAi-mediated approaches and liver-targeted gene therapy. Current therapy options for AIP mainly include the administration of carbohydrates, haem arginate, or haemin (an iron-containing porphyrin), depending on the severity of the attack.
Fig. 1 A schematic overview of the current and ongoing efforts in the therapy of AIP and their therapeutical targets. (Longo M, et al., 2022)
Our Services
Our company's animal models and disease modeling services offer several advantages for AIP researchers. We are committed to helping our clients develop customized models tailored to specific research needs to advance the field of AIP research. We offer a wide range of services, including gene editing, phenotyping, and preclinical testing, to support all stages of drug development. Our disease modeling services include, but are not limited to:
- Generation of AIP mouse model
We provide clients with three different AIP transgenic mouse models with PBGD gene mutations, which have varying degrees of defects in PBGD activity.
Transgenic mouse (T1) models. We generate Pbgd–/– mice by inserting the neo gene in an antisense direction into the SacII site of the first exon.
Transgenic mouse (T2) models. We generate Pbgd+/– mice by inserting a splice acceptor site in front of the coding sequence of the neo gene, which is then inserted into the first intron of Pbgd.
Compound heterozygote of T1 and T2 mouse models.
We also provide our clients with homozygous dominant AIP (HD-AIP) mouse models. We generated R167Q+/+ mice by gene targeting, and these models exhibit severe neurological abnormalities similar to human HD-AIP disease.
- AIP feline model
We provide our clients with naturally occurring feline models of AIP to further investigate the pathogenesis of acute, life-threatening neurological attacks in human AIP.
Our Solutions
Our animal models can be utilized for a range of potential therapeutic studies and obtainmeaningful and promising data. Our solutions include:
- Development of animal models for the evaluation ofliver-targeted gene therapies for AIP, such as adenoviral and adeno-associated viral (AAV)-mediated strategies.
- Development of animal models for preclinical research of short interfering RNA (siRNA) encapsulated in lipid nanoparticles (LNP) specifically targeting hepatic Alas1 (Alas1-siRNA).
- Development of animal models for the preclinicalstudy of PBGD mRNA therapy.
- Development of animal models for disease pharmacokinetic–pharmacodynamic modeling.
Our company is a leading provider of animal models and disease modeling services, with a team of experts specializing in animal model generation and preclinical in vivo drug testing. We are well-positioned to help our clients develop animal models that mimic the human AIP phenotype and provide scientific guidance in model selection, preclinical study design, and endpoint analysis. If you are interested in our disease modeling services, please contact us for more information.
Reference
- Longo, M.; et al. Cutting-edge therapies and novel strategies for acute intermittent porphyria: step-by-step towards the solution. Biomedicines, 2022, 10(3): 648.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
